DiPOA ([8-(3,3-diphenyl-propyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]dec-3-yl]-acetic acid), a novel, systemically available, and peripherally restricted Mu opioid agonist with antihyperalgesic activity: II. In vivo pharmacological characterization in the rat.

Mu opioid receptors are expressed throughout the central and peripheral nervous systems. Peripheral inflammation leads to an increase in mu receptor present on the peripheral terminals of primary sensory neurons. Activation of peripheral mu receptors produces potent antihyperalgesic effects in both humans and animals.

Alterations in brain metabolism induced by chronic morphine treatment: NMR studies in rat CNS.

High-resolution (500 MHz) multiresonance/multinuclear proton (1H) nuclear magnetic resonance (NMR) spectroscopy was used to detect metabolic changes and cellular injury in the rat brain stem and spinal cord following chronic morphine treatment. Compensatory changes were observed in glycine, glutamate, and inositols in the brain stem, but not the spinal cord, of chronic morphine-treated rats. In spinal cord, increases were detected in lactate and N-acetyl-aspartate (NAA), suggesting that there is anaerobic glycolysis, plasma membrane damage, and altered pH preferentially in the spinal cord of chronic morphine-treated rats.

Antisense oligonucleotide knockdown of mGluR1 alleviates hyperalgesia and allodynia associated with chronic inflammation.

Chronic inflammation induced by injection of complete Freund's adjuvant (CFA) into one hindpaw elicits thermal hyperalgesia and mechanical allodynia in the injected paw. Metabotropic glutamate receptors (mGluRs) have been implicated in dorsal horn neuronal nociceptive responses and pain associated with short-term inflammation. The goal of the present study was to assess the role of mGluR1 in the hyperalgesia and allodynia associated with the CFA model of chronic inflammation.

Attenuation of morphine tolerance after antisense oligonucleotide knock-down of spinal mGluR1.

1. Chronic systemic treatment of rats with morphine leads to the development of opioid tolerance. This study was designed to examine the effects of intrathecal (i.

Intrathecal administration of the mGluR compound, (S)-4CPG, attenuates hyperalgesia and allodynia associated with sciatic nerve constriction injury in rats.

The present study examined the effects of intrathecal (i.t.) treatment (twice-daily injections on post-operative (PO) days 0-8) with the metabotropic glutamate receptor (mGluR) compound, (S)-4-carboxyphenylglycine ((S)-4CPG), or the non-competitive N-methyl-D-aspartate (NMDA) antagonist, dizocilipine maleate (MK-801), on mechanical allodynia and cold hyperalgesia associated with chronic constriction injury (CCI) of the sciatic nerve in rats.

The formalin test: a validation of the weighted-scores method of behavioural pain rating.

The formalin test was developed using an ordinal scale of weighted scores to rate the intensity of pain-related behaviours in animals. However, no studies have been carried out to establish the ordinal relationship of the behavioural categories used to generate the weighted pain intensity scores. The purpose of the present study was to evaluate the validity of the weighted-scores technique by assessing the ordinality of the behavioural categories associated with the specific category weights.